The never-ending sickness

Famous cities such as Rome may keep their semi-empty look for months to come.

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cientists around the globe are scrambling to find a pharmacological fix for COVID-19, the disease caused by the world-stopping coronavirus that emerged from a landlocked Chinese province in late December. It has already claimed tens of thousands of lives and is likely to take many more.

The disease wreaks havoc on the human respiratory system, often swiftly killing patients who already have pneumonia. Since January, when the disease began its westward move from China, more than a million cases have been confirmed globally with more than 50,000 deaths, nearly a fourth of that figure in Italy. Though the possibility of a widespread pandemic was always feared by medical authorities, particularly as the world became more interconnected, COVID-19 represents the most massive international visitation of the 21st century, coming almost exactly a century after the so-called Spanish Flu killed tens of millions immediately after the end of World War I.

There’s been so much confusion, and so much ballyhooing of false leads that I decided to look closely at the candidate medications, with help from medical sources I consider both authoritative and current.

Sadly, what I’ve found so far is mostly hype.

Chloroquine:

Doctors are hoarding antimalarial medications for themselves and their families, shrinking the supply to the point that lupus patients can’t fill their prescriptions. A few poor souls are killing themselves with chloroquine phosphate fish bowl cleaner.

The idea that this drug might help received a big boost from Donald Trump, who recently suggested it as a virus-stopper.

The drug inhibits coronavirus in vitro and is already FDA-approved, which would make it immediately available.

But that’s end of the positive news. Trials in China were rumored to be promising, but for weeks the original reports weren’t available. When scientists finally found them, the drug turned out to have done no better than placebo.

Until an effective vaccine proves itself (think next year), the best bet lies in taking shelter at home.

The only Western researchers, in France, claimed that 20 patients treated with hydroxychloroquine cleared nasopharyngeal coronavirus faster than 16 patients who received standard treatment alone.

That’s fine until you examine the paper and its results, which to my eye contained no “clinical status” subsection.

A more careful reader found this information in a subsection entitled “Demographics.” It turns out the French researchers had given hydroxychloroquine not to 20 but to 26 patients, and the patients who received the drug actually did worse than controls: three needed to be transferred to ICU units and a fourth died (two others withdrew).

No control patient had these outcomes. These damning results suggest the researchers intentionally buried their clinical findings.

Umifenovir: This Russian flu drug was tested, along with Oseltamivir, and flopped.

Baloxavir: Currently undergoing several “Why not?” clinical trials, though expectations are low.

Niclosamide: This deworming medicine showed some anti-SARS effect in vitro but never went on to clinical trials.

Corticosteroids:

Steroids have been used for years as a kind of hail-Mary pass in patients with septic shock, making it reasonable to try them in end-stage COVID-19. One Chinese study of methylprednisolone suggested benefit, but international expert consensus says corticosteroids are likely to do more harm than good.

Azithromycin:

This was tested in COVID-19 patients, together with hydroxychloroquine, to counter super-infection without any evidence of clinical benefits.

Other medications:

Several FDA-approved drugs are currently being studied on theoretical grounds, with no evidence and little hope they will yield positive results. They include inhaled nitric oxide, vitamin C ,and losartan (which some fear may make the disease worse, not better).

Where would I put my money?

Until an effective vaccine proves itself (think next year), the best bet lies in taking shelter at home.

Remdesivir:

Effective against a variety of coronavirus species, remdesivir is widely considered the most promising antiviral for COVID-19 and is undergoing many trials.

It is used in Italian hospitals, and drug-maker Gilead is expanding its availability for compassionate use.

Favipiravir:

This Japanese antiviral improved recovery and chest imaging in trials involving 340 Chinese patients and is undergoing further study. It is approved for compassionate use in Italy, but is not available in the United States.

Convalescent serum:

Shortly before the antibiotic era, convalescent serum was the mainstay for treating infection. Passive immunity —whole blood, plasma, or immunoglobulin — which was the only useful drug treatment for Ebola, might not only treat COVID-19 but also protect front-line health care workers. The Chinese carried immune serum to Italy, but both Italy and the U.S. now have enough recovered patients to produce their own. Treatment trials are about to start, while researchers work to develop serological tests for identifying additional donors.

Tocilizumab:

This anti-interleukin-6 biologic for rheumatoid arthritis might help dam down on the local inflammatory response in COVID-19 pneumonia. Unfortunately tocilizumab promotes many serious infections, so it can only be used in the most desperate cases. Roche is beginning a Phase III study, while Sanofi tests a similar drug known as sarilumab.

Interferon:

Injected interferon-beta has shown promise in coronavirus diseases, and may suppress viral multiplication, though at the cost of substantial toxicity. It is undergoing clinical trials. But an inhaled formulation of the same drug, code named SNG001, might give similar benefits with fewer complications. It has been reported to hasten recovery of asthma and chronic obstructive pulmonary disease (COPD) patients with pneumonia. Testing against COVID-19 has begun in the United Kingdom.

So what’s the final solution?

The real hope is that social distancing and medication will place us in a holding pattern until an effective coronavirus vaccine can knock out the pandemic. Groups in a half-dozen countries have developed candidate vaccines, and several volunteers have already received doses, usually in the spirit of international cooperation.

Not always, though. Trump has made it clear he wants the winning vaccine to be produced on American soil. He tried luring Germany’s CureVac to move to the U.S. for research and production. This would guarantee Americans monopoly rights to any breakthrough. Apparently the German government had to intervene to stop this. At best, it will be autumn 2021 before an effective vaccine can be administered to enough people that herd immunity will protect the uninfected.

So for now our best bet lies in taking shelter at home. Fortunately, there’s double good news on that front. One is that social distancing measures seem to be effective even if they are less than draconian, or even consistent.

Another piece of good news is that a month after northern Italy was locked down, my adoptive country’s epidemic is slowing down, and that is a very hopeful sign.

New York native Susan Levenstein, MD, moved to Italy in 1978 and has maintained a successful Rome primary care practice since 1980. She has a professional website and writes a blog. In May 2019, Paul Dry Books published her memoirs, entitled "Dottoressa".

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